Investigation of the mechanisms of lung diseases, such as asthma and cystic fibrosis, involves understanding the roles of the smooth muscle and the epithelium of the airway (trachea). The smooth muscle controls the airway diameter, while the epithelium regulates ionic composition of the liquid lining the airway through electrogenic ion transport and releases factors that regulate the ability of the smooth muscle to contract. Various techniques and apparatus are known for stimulating an intact trachea or a tracheal segment in vitro and for measuring smooth muscle activity and bioelectric properties of the epithelium in response to the stimuli.
One known technique for measuring the contraction and relaxation of the airway smooth muscle involves mounting an intact trachea to a perfusion device for flowing a perfusion liquid through the trachea. The perfusion device has an inlet cannula extending into one end of the trachea and an outlet cannula extending into the opposite end of the trachea. A differential pressure device fluidly connected to the cannulas measures the differential pressure of the perfusion liquid flowing through the trachea (e.g., the inlet pressure minus the outlet pressure), which is a direct index of the airway diameter. The inner epithelial surface or the outer serosal surface is stimulated by adding agents to the perfusion liquid or an extraluminal bath in which the trachea is disposed. The differential pressure device is used to detect changes in the airway diameter in response to the stimuli. A drawback of this technique is that there is no provision for measuring bioelectric properties of the epithelium, such as the electrical potential across the epithelium (transepithelial potential difference) and the impedance of the epithelium (transepithelial impedance).
In an improvement of the foregoing technique, the perfusion device and trachea are placed in an extraluminal bath containing a voltage electrode. Another voltage electrode is placed in the perfusion line supplying the perfusion liquid to the trachea. The voltage electrodes are used to measure the transepithelial potential difference of the trachea. As described above, a differential pressure device can be used to measure the differential pressure of the perfusion liquid flowing through the trachea. While an improvement of prior devices, this technique suffers from the disadvantage that there is no provision for measuring the transepithelial impedance of the trachea.
A common technique for simultaneously measuring the transepithelial potential and transepithelial impedance of a trachea involves placing a small, flattened strip of trachea in an in vitro apparatus known as an “Ussing” chamber. The chamber has separate ports for connecting voltage electrodes and current electrodes. The voltage electrodes measure the transepithelial potential difference of the trachea segment, while the current electrodes pass a current through the trachea segment to permit measurement of the transepithelial impedance. Unfortunately, this technique cannot be used for measuring smooth muscle activity of the trachea. Moreover, the cylindrical tracheal wall becomes distorted when it is flattened and clamped inside the Ussing chamber.
Heretofore, prior devices have not allowed for the measurement of smooth muscle activity, transepithelial potential difference and transepithelial impedance of a single trachea preparation. Accordingly, there is a continuing need for improved apparatus and methods for measuring characteristics of a trachea.